This invention concerns the preparation of fluorinated compounds that can be used as building blocks for fluorinated organics. For example, the trifluoromethyl group occurs in many biologically active compounds such as herbicides and biocides. Many new drugs are specifically functionalized fluorinated organics, such as flecainide acetate, a cardiac antiarrhymthmic agent.
Generally, prior procedures for preparing fluorinated compounds use hydrogen fluoride as the fluorinating agent in a halogen/fluorine exchange. Often, this step occurs late in a synthetic sequence and the desired selectivity is not always obtained. Methods which use other fluorinated precursors may be selective but the cost of the reagent is usually prohibitively high for commercial preparation. Trifluoroacetic acid and trifluoroethanol are reagents which are expensive as building block precursors.
The present invention specifically relates to the generation of trifluoroethanol and trifluoroacetic acid from trifluoromethyl chloride. Trifluoromethyl chloride is an inexpensive starting material as it is a by-product from dichlorodifluoromethane manufacture.
Procedures are known for carboxylation of some perfluoroalkyl iodides. Blaneou et al., J.C.S. Chem. Comm., Vol. 1976, pp 885-886 (1976) prepared perfluorobutanoic, perfluorohexanoic and perfluorooctanoic acids using reaction with carbon dioxide in a Zn-Cu dispersion. Percentage yields, however, were moderate, ranging from 40%-63%.
Ishikawa et al, J. Fluorine Chem., Vol. 22, pp. 585-587 (1983), similarly used chemical means to carboxylate perfluoroalkyl iodides. The reaction, using the n-octyl, n-hexyl, n-butyl and i-propyl perfluoroiodide, were ultrasound-promoted in the presence of zinc powder. Percentage yields of acid ranged from 48-77%. Calas et al., J. Electroanal. Chem. Vol. 89, pp. 363-372 (1978), prepared perfluorohexanoic acid by electroreduction of perfluoro-n-hexyl iodide, using a mercury electrode and lithium chloride as the supporting electrolyte in dimethylformamide, and bubbling in carbon dioxide. Yields over 90% were reported, but with some uncertainty noted. Carboxylation was found to depend strongly on the supporting electrolyte used. For example, no electrocarboxylation occurred when lithium perchlorate was used. Alkyl chlorides are generally recognized as having lower reactivities than alkyl iodides and alkyl bromides, (see e.g. Fieser and Fieser, Advanced Organic Chemistry, p. 341 (1961)). Moreover, trifluoromethyl chloride, in contrast to trifluoromethyl iodide, is a low boiling gaseous material which is poorly soluble in solvents such as dimethyl formamide.
Baizer et al (Tetrahedron Let., No. 47, pp 4809-4812, (1972)) reported production of esters, carbonates, mercuric compounds and oxalates from the reduction of alkyl halides and carbon dioxide at a mercury electrode. With n-pentylchloride, small amounts of pentyl hexanoate and bipentyl carbonate were reported, but with an oxalate as the major product. A related Baizer and Wagenknecht Pat. No. 3,764,492 similarly reports electrolysis results, principally at a mercury electrode. Substantial yields were apparently obtained with activated labile halide compounds, such as benzyl chloride and allyl chloride, but only a small amount of pentyl hexanoate identified by chromatographic analysis was reported for an example using 1-chloropentane, the only alkyl chloride example reported. In the Baizer work, esters produced, such as pentyl hexanoate from pentyl chloride, involved two molecules of alkyl halide reactant for each molecule of ester product. It is fortunate that a similar esterification reaction does not occur in the present process, at least to any great extent under the conditions utilized, as such an esterification would use up half of the expensive perfluoro reactant in forming an ester moiety. In the present process, an inexpensive agent, such as methyl chloride, serves very well as an esterifying agent. U.S. Pat. No. 3,764,492 further suggests that additional halide groups in the reactant may result in the production of polyesters.